Many properties and changes that occur in cells are a result of the types of proteins present in the cells. The structural and functional state of chromatin is thought to determine the types of proteins being synthesized and should reflect, at a fundamental but general level, the functional state of a cell. Moreover, the condition of chromatin should provide a basic parameter describing th physiological state of an rgan as one functional unit. Thus, an age-related determination and comparison of the structure and biochemistry of chromatin from mammalian tissues should be of value in answering questions about the general loss of health associated with senescence and about possible primary aging processes. We propose to study mammalian aging by examining age-associated changes in chromatin. Using an inbred rodent model-system, we intend to: (1) determine the longevity of histones; (2) probe for alterations in histone structure; (3) dissect chromatin to search for structural changes; (4) reexamine previous physiochemical characterizations of chromatin; and, (5) examine chromatin for possible DNA-protein, histone-histone, and DNA-DNA cross-links. In addition to the biochemical and physical investigation, we also propose to research the physiology of chromatin by comparing histone modification (acetylation) and DNA repair as a function of age.